Optimal Degradation Rate for Collagen Chambers Used for Regeneration of Peripheral Nerves over Long Gaps

Abstract

The experimental study of peripheral nerve regeneration has depended heavily on the use of a nerve chamber in which the stumps of the transected nerve are inserted. A large variety of chamber fillings and chamber types have been used in an effort to induce a higher quality of regeneration across the gap initially separating the two stumps. In this study we studied the morphology of nerves regenerated across a 15 mm gap following implantation of a series of five chambers. The chambers were fabricated from type I collagen and possessed identical pore volume fractions as well as average pore diameters, but differed in cross-link density continuously along the series. The residual mass of the implanted chambers at 9 weeks was observed to increase continuously with increasing cross-link density along the series, indicating a continuous decrease in degradation rate. The quality of regenerated nerves, determined by the number of large diameter fibers (A-fibers) per nerve, the average diameter of all axons and the ratio of area occupied by axons (N-Ratio), was superior at an intermediate level of chamber degradation rate. The maximal quality of peripheral nerve regeneration corresponded to an optimal degradation rate with an estimated chamber half-life of approximately 2–3 weeks following implantation. A speculative mechanistic explanation of the observed optimum focuses on the hypothetical role of cell and cytokine traffic that may take place through holes in the chamber generated by the degradation process. The data show the presence of a hitherto unreported optimal chamber degradation rate that leads to regenerated nerves of maximum quality.

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

“…The fibrillar structure of the collagen is maintained throughout manufacture, permitting construction of a tubular matrix that has excellent mechanical strength and defined permeability. 3,30,45 The level of functional recovery achieved with the NeuraGen conduit has been equivalent to direct suture repair of short-segment defects in several experiments in both rats and primates. 4 The use of NeuraGen nerve guides in combination with cultured autologous SCs could expand the clinical potential of the nerve guide, permitting the repair of a larger array of peripheral nerve injuries, even those with a lengthy gap.…”

“…67 To circumvent this potential problem, Lewis rats could be used as an alternative for future walking track studies, since it has been suggested that this strain is less prone to autophagia than are Fischer rats. 12,21,30,39 Our laboratory has performed reversed autografts in male Lewis rats by following the same protocol applied in the current study, with 4-and 16-week survival times. The Lewis rats displayed little to no autotomy behavior.…”

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

“…Collagen-glycosaminoglycan (CG) scaffolds are regulatory compliant ECM analogs that have been applied to a wide range of regenerative medicine applications, both in vivo for soft tissue applications such as dermis, peripheral nerves, conjunctiva, brain, and cartilage [9][10][11][12] as well as in vitro as three-dimensional (3D) templates to probe various cellular activities, including adhesion, proliferation, migration, and differentiation. [13][14][15][16][17] CG scaffolds have also been adapted for a variety of orthopedic applications covering osteochondral, bone, and tendon tissue engineering.…”

Dynamic, 3D‐Pattern Formation Within Enzyme‐Responsive Hydrogels

“…For example, in peripheral nerve regeneration applications, it has been hypothesized that hydrogel implants must be degradable to avoid physical inhibition of nerve growth and that the optimal degradation half-life of these implants should match the rate of nerve regeneration, approximately 2-4 weeks. [32][33][34][35] In an effort to mimic potential physiological conditions present in such neuronal applications, biologically relevant tPA and uPA concentrations were approximated by performing an enzymelinked immunosorbent assay (ELISA) on PC-12 neuronal-like culture supernatants. These decreased enzyme conditions resulted in the predictable extension of scaffold degradation rate trends over a one-month period and place our hydrogels within the proposed optimal degradation rate range for neuronal materials (Fig.…”